Pergsmn Press Printed in the U.S.A. CHANGES IN STRUCTURAL INTEGRITY OF HEART DNA FROM AGING MICE

The state of the structural integrity of the DNA from mouse myocardial cells has been investigated by utilizing both CaCl density gradient sedimentation and digestion by S1 eadonucleasa from Aspergillus orzae. The DNA from myocardial cells of young mice 3sedimeated inânarrow peak at the ezpected density of 1.701 g/cm, while the DNA from the heart cells of senescent mice became broadly distributed is CaCl gradients, banding even more multimodally is alkaline sucrose gradients. This mode of sedimentation indicates that old mouse DNA becomes partially fragneated. When the native DNA of myocardial calls from 6, 20 and 30 month old mice was treated with single-strand specific S endonuclease, it was the DNA from the senescent mice that showéd a progressive increase in sensitivity to digestion by the enzyme. The results indicate that the heart DNA of aging mice develops single-stranded gaps in addition to a breakdown into differently sized fragments. The survival of a given species is moat successfully assured by the main-tenance of the structural integrity of its geaome. As a provision for this metabolic raquirsmeat, cells are equipped with enzymes whose function is to catalyze the repair-replication of damaged DNA (1). This unscheduled DNA synthesis is crucial for the preservation of the structural integrity of DNA. Hart and Setlow (2) used W irradiation studies to show that those animals whose irradiated cells possess a greater capacity for DNA repair-replication have a longer life spas. A different way of easmining the validity of their observation is to determine both the levels of DNA repair enzyme activities and the geaome integrity in the cells of aging animals. This problem can be more fruitfully imrestigated in poet-mitotic cells such as neurons, muscle cells and heart cells (3). These nondividing cells need DNA repair enzymes to correct say damage that may occur in their DNA, Tha present communication reports the results which we obtained is our ez~ination of the state of muse cardiac cell DNA during senescence